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Fra-2/AP-1 通过调节成骨细胞分化和胶原生成来控制骨形成。

Fra-2/AP-1 controls bone formation by regulating osteoblast differentiation and collagen production.

机构信息

Genes, Development, and Disease Group, BBVA Foundation, Cancer Cell Biology Program, Spanish National Cancer Center, E-28029 Madrid, Spain.

出版信息

J Cell Biol. 2010 Sep 20;190(6):1093-106. doi: 10.1083/jcb.201002111. Epub 2010 Sep 13.

DOI:10.1083/jcb.201002111
PMID:20837772
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3101588/
Abstract

The activator protein-1 (AP-1) transcription factor complex, in particular the Fos proteins, is an important regulator of bone homeostasis. Fra-2 (Fosl2), a Fos-related protein of the AP-1 family, is expressed in bone cells, and newborn mice lacking Fra-2 exhibit defects in chondrocytes and osteoclasts. Here we show that Fra-2-deficient osteoblasts display a differentiation defect both in vivo and in vitro. Moreover, Fra-2-overexpressing mice are osteosclerotic because of increased differentiation of osteoblasts, which appears to be cell autonomous. Importantly, the osteoblast-specific osteocalcin (Oc) gene and collagen1α2 (col1α2) are transcriptional targets of Fra-2 in both murine and human bone cells. In addition, Fra-2, Oc, and col1 are expressed in stromal cells of human chondroblastic and osteoblastic osteosarcomas (Os's) as well as during osteoblast differentiation of human Os cell lines. These findings reveal a novel function of Fra-2/AP-1 as a positive regulator of bone and matrix formation in mice and humans.

摘要

激活蛋白-1 (AP-1) 转录因子复合物，特别是 Fos 蛋白，是骨稳态的重要调节因子。AP-1 家族的 Fos 相关蛋白 Fra-2 (Fosl2) 在骨细胞中表达，新生 Fra-2 缺失的小鼠表现出软骨细胞和成骨细胞缺陷。本文显示 Fra-2 缺陷的成骨细胞在体内和体外均表现出分化缺陷。此外，Fra-2 过表达小鼠由于成骨细胞分化增加而出现骨质硬化，这似乎是细胞自主性的。重要的是，成骨细胞特异性的骨钙素 (Oc) 基因和胶原 1α2 (col1α2) 是 Fra-2 在小鼠和人骨细胞中的转录靶标。此外，Fra-2、Oc 和 col1 在人成软骨和成骨骨肉瘤 (Os) 的基质细胞以及人 Os 细胞系的成骨细胞分化过程中表达。这些发现揭示了 Fra-2/AP-1 在小鼠和人类中作为骨和基质形成的正调节剂的新功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/185cc99eefb5/JCB_201002111_RGB_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/c8b80ab6254a/JCB_201002111_RGB_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/45a764d0bfdc/JCB_201002111_RGB_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/a59fbe2b2c59/JCB_201002111RR_RGB_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/2b5c1a215fd3/JCB_201002111_RGB_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/c841736abece/JCB_201002111_RGB_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/185cc99eefb5/JCB_201002111_RGB_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/c8b80ab6254a/JCB_201002111_RGB_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/45a764d0bfdc/JCB_201002111_RGB_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/a59fbe2b2c59/JCB_201002111RR_RGB_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/2b5c1a215fd3/JCB_201002111_RGB_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/c841736abece/JCB_201002111_RGB_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b866/3101588/185cc99eefb5/JCB_201002111_RGB_Fig6.jpg

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